Nanoelectrode‐Mediated Extracellular Electrical Stimulation Directing Dopaminergic Neuronal Differentiation of Stem Cells for Improved Parkinson's Disease Therapy

Abstract Parkinson's disease (PD) is a neurodegenerative disease caused by the dysfunction and death of dopaminergic neurons. Neural‐stem‐cell (NSC)‐based therapy is a promising approach for the treatment of PD but its therapeutic performance is limited by low efficiency of differentiation of NSCs to dopaminergic neurons. Although electrical stimulation can promote neuronal differentiation, it is not verified whether it can induce the NSCs to specifically differentiate into dopaminergic neurons. Meanwhile, it is a great challenge to precisely apply electrical stimulation to dynamically migrating NSCs after transplantation. Here, electrochemically exfoliated graphene nanosheets are designed to anchor to the membrane of NSCs to serve as wireless nanoelectrodes. After anchoring to the cell membrane, these nanoelectrodes are able to migrate together with the cells and precisely apply extracellular electrical stimulation to the receptors or ion transport channels on the membrane of transplanted cells under alternating magnetic field. The nanoelectrode‐mediated electrical stimulation induces 38.46% of the NSCs to specifically differentiate into dopaminergic neurons, while the percentage is only 5.82% for NSCs without the nanoelectrode stimulation. Transplantation of NSCs anchored with the nanoelectrodes effectively improves the recovery of the motor and memory ability of PD mice under alternating magnetic field within 2 weeks.